This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [provided by RefSeq, Jul 2008] See more...

Aliases for SESN2 Gene

Aliases for SESN2 Gene

  • Sestrin 2 2 3 5
  • SEST2 2 3 4
  • Sestrin-2 3 4
  • HI95 2 3
  • SES2 2 3
  • Hypoxia Induced Gene 95 3
  • Hypoxia-Induced Gene 4
  • Hypoxia-Induced 3
  • DKFZp761M0212 2
  • EC 1.11.1.- 4
  • SESN2 5
  • Hi95 4

External Ids for SESN2 Gene

Previous GeneCards Identifiers for SESN2 Gene

  • GC01P027819
  • GC01P028190
  • GC01P028458
  • GC01P028586
  • GC01P026842

Summaries for SESN2 Gene

Entrez Gene Summary for SESN2 Gene

  • This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [provided by RefSeq, Jul 2008]

GeneCards Summary for SESN2 Gene

SESN2 (Sestrin 2) is a Protein Coding gene. Diseases associated with SESN2 include Nodular Ganglioneuroblastoma and Pulmonary Emphysema. Among its related pathways are Gene Expression and mTOR signaling pathway (KEGG). An important paralog of this gene is SESN1.

UniProtKB/Swiss-Prot Summary for SESN2 Gene

  • Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821).

Gene Wiki entry for SESN2 Gene

Additional gene information for SESN2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SESN2 Gene

Genomics for SESN2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SESN2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SESN2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SESN2

Top Transcription factor binding sites by QIAGEN in the SESN2 gene promoter:
  • CREB
  • deltaCREB
  • GATA-1
  • GATA-2
  • GATA-3
  • HSF2
  • NF-kappaB
  • p53
  • Pax-3
  • RREB-1

Genomic Locations for SESN2 Gene

Genomic Locations for SESN2 Gene
chr1:28,259,452-28,282,491
(GRCh38/hg38)
Size:
23,040 bases
Orientation:
Plus strand
chr1:28,585,963-28,609,002
(GRCh37/hg19)
Size:
23,040 bases
Orientation:
Plus strand

Genomic View for SESN2 Gene

Genes around SESN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SESN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SESN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SESN2 Gene

Proteins for SESN2 Gene

  • Protein details for SESN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P58004-SESN2_HUMAN
    Recommended name:
    Sestrin-2
    Protein Accession:
    P58004
    Secondary Accessions:
    • Q5T7D0
    • Q96SI5

    Protein attributes for SESN2 Gene

    Size:
    480 amino acids
    Molecular mass:
    54494 Da
    Quaternary structure:
    • Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (PubMed:25263562, PubMed:25457612, PubMed:26449471). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (By similarity). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:23274085, PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (PubMed:15105503).
    SequenceCaution:
    • Sequence=BAB55438.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SESN2 Gene

neXtProt entry for SESN2 Gene

Post-translational modifications for SESN2 Gene

Other Protein References for SESN2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SESN2 Gene

Domains & Families for SESN2 Gene

Gene Families for SESN2 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for SESN2 Gene

InterPro:
Blocks:
  • PA26 p53-induced protein (sestrin)
ProtoNet:

Suggested Antigen Peptide Sequences for SESN2 Gene

GenScript: Design optimal peptide antigens:
  • Hi95 (SESN2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P58004

UniProtKB/Swiss-Prot:

SESN2_HUMAN :
  • Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling.
  • Belongs to the sestrin family.
Domain:
  • Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling.
Family:
  • Belongs to the sestrin family.
genes like me logo Genes that share domains with SESN2: view

Function for SESN2 Gene

Molecular function for SESN2 Gene

UniProtKB/Swiss-Prot Function:
Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[protein]-dithiol + a hydroperoxide = [protein]-disulfide + an alcohol + H2O; Xref=Rhea:RHEA:10008, Rhea:RHEA-COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:50058; Evidence={ECO:0000305|PubMed:26612684};.
UniProtKB/Swiss-Prot Induction:
Up-regulated by hypoxia and DNA damage (PubMed:12203114). Up-regulated by treatments inducing endoplasmic reticulum stress (PubMed:24947615).

Enzyme Numbers (IUBMB) for SESN2 Gene

Phenotypes From GWAS Catalog for SESN2 Gene

Gene Ontology (GO) - Molecular Function for SESN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005092 GDP-dissociation inhibitor activity IEA --
GO:0005515 protein binding IPI 15105503
GO:0016491 oxidoreductase activity IEA --
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor IBA,IDA 26612684
GO:0032542 NOT sulfiredoxin activity IDA 19113821
genes like me logo Genes that share ontologies with SESN2: view
genes like me logo Genes that share phenotypes with SESN2: view

Animal Model Products

CRISPR Products

miRNA for SESN2 Gene

miRTarBase miRNAs that target SESN2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN2

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for SESN2 Gene

Localization for SESN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SESN2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SESN2 gene
Compartment Confidence
cytosol 5
nucleus 4
mitochondrion 3
plasma membrane 2
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SESN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA,IDA 15105503
GO:0005739 mitochondrion IEA --
GO:0005829 cytosol TAS --
GO:0031588 colocalizes_with nucleotide-activated protein kinase complex IEA,ISS --
genes like me logo Genes that share ontologies with SESN2: view

Pathways & Interactions for SESN2 Gene

genes like me logo Genes that share pathways with SESN2: view

Pathways by source for SESN2 Gene

1 Cell Signaling Technology pathway for SESN2 Gene

Gene Ontology (GO) - Biological Process for SESN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001932 regulation of protein phosphorylation IEA,IDA 25040165
GO:0006111 regulation of gluconeogenesis IEA --
GO:0006635 fatty acid beta-oxidation IEA --
GO:0007005 mitochondrion organization IEA --
GO:0009749 response to glucose IEA --
genes like me logo Genes that share ontologies with SESN2: view

No data available for SIGNOR curated interactions for SESN2 Gene

Drugs & Compounds for SESN2 Gene

No Compound Related Data Available

Transcripts for SESN2 Gene

mRNA/cDNA for SESN2 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN2

Alternative Splicing Database (ASD) splice patterns (SP) for SESN2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b
SP1:
SP2: -

Relevant External Links for SESN2 Gene

GeneLoc Exon Structure for
SESN2

Expression for SESN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SESN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SESN2 Gene

This gene is overexpressed in Liver (20.9), Testis (15.0), Islet of Langerhans (11.5), and Pancreas (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SESN2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SESN2

SOURCE GeneReport for Unigene cluster for SESN2 Gene:

Hs.469543

mRNA Expression by UniProt/SwissProt for SESN2 Gene:

P58004-SESN2_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for SESN2 Gene

  • Nervous system(4.6)
  • Muscle(4.5)
  • Liver(4.5)
  • Heart(2.7)
  • Kidney(2.6)
  • Skin(2.5)
  • Intestine(2.5)
  • Blood(2.3)
  • Pancreas(2.3)
  • Bone marrow(2.2)
  • Eye(2.2)
  • Lymph node(2)
  • Spleen(2)
genes like me logo Genes that share expression patterns with SESN2: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SESN2 Gene

Orthologs for SESN2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SESN2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SESN2 30 31
  • 99.36 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SESN2 30 31
  • 90.51 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SESN2 30 31
  • 90.42 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Sesn2 30 17 31
  • 88.06 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sesn2 30
  • 87.85 (n)
Oppossum
(Monodelphis domestica)
Mammalia SESN2 31
  • 76 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SESN2 31
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SESN2 31
  • 62 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SESN2 31
  • 66 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sesn2 30
  • 63.16 (n)
Zebrafish
(Danio rerio)
Actinopterygii sesn2 30 31
  • 63.55 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Sesn 31
  • 41 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea sesn-1 31
  • 25 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.3472 31
  • 30 (a)
OneToMany
Species where no ortholog for SESN2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SESN2 Gene

ENSEMBL:
Gene Tree for SESN2 (if available)
TreeFam:
Gene Tree for SESN2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SESN2: view image

Paralogs for SESN2 Gene

Paralogs for SESN2 Gene

(2) SIMAP similar genes for SESN2 Gene using alignment to 1 proteins:

  • SESN2_HUMAN
genes like me logo Genes that share paralogs with SESN2: view

Variants for SESN2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SESN2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
711836 Benign: not provided 28,273,441(+) G/A SYNONYMOUS_VARIANT
718968 Benign: not provided 28,274,096(+) A/G MISSENSE_VARIANT
720740 Benign: not provided 28,273,387(+) G/A SYNONYMOUS_VARIANT
721173 Likely Benign: not provided 28,269,198(+) C/T MISSENSE_VARIANT
721204 Benign: not provided 28,271,776(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for SESN2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SESN2 Gene

Variant ID Type Subtype PubMed ID
esv994212 CNV deletion 20482838
nsv545916 CNV gain 21841781
nsv545917 CNV loss 21841781
nsv545918 CNV loss 21841781

Variation tolerance for SESN2 Gene

Residual Variation Intolerance Score: 53.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.74; 46.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SESN2 Gene

Human Gene Mutation Database (HGMD)
SESN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SESN2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SESN2 Gene

Disorders for SESN2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for SESN2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
nodular ganglioneuroblastoma
  • ganglioneuroblastoma, nodular
pulmonary emphysema
endometrial adenosquamous carcinoma
  • adenosquamous carcinoma of endometrium
tuberous sclerosis 2
  • ts
breast cancer
  • breast lobular carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search SESN2 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with SESN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SESN2 Gene

Publications for SESN2 Gene

  1. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. (PMID: 15105503) Budanov AV … Chumakov PM (Science (New York, N.Y.) 2004) 3 4 23
  2. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. (PMID: 12607115) Peeters H … Devriendt K (Human genetics 2003) 2 3 4
  3. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. (PMID: 12203114) Budanov AV … Feinstein E (Oncogene 2002) 2 3 4
  4. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. (PMID: 26586190) Saxton RA … Sabatini DM (Science (New York, N.Y.) 2016) 3 4
  5. Sestrin2 is a leucine sensor for the mTORC1 pathway. (PMID: 26449471) Wolfson RL … Sabatini DM (Science (New York, N.Y.) 2016) 3 4

Products for SESN2 Gene

Sources for SESN2 Gene